The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature‐controlled shelf

Searles, James A.; Carpenter, John F.; Randolph, Theodore W.

doi:10.1002/jps.1039

Cited by 335 publications

(256 citation statements)

References 28 publications

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“…In all cases, sample size was approximately 10 mg. Cooling and warming rates were 28C min 21 . The samples were initially held at 258C and cooled down to 2258C.…”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

“…Large set cooling rates, often produced by liquid nitrogen quenching, can alter the pore anisotropy by creating large temperature gradients within the volume of the slurry [8]. On the other hand, moderate set cooling rates have no power to alter the isotropy of a scaffold structure, although shifts between 0.6 and 0.98C min 21 have been shown to change the pore size between 120 and 90 mm, respectively [9]. The final pore structure, whether anisotropic or isotropic, is determined not only by the nucleation of ice but also by the subsequent growth of ice crystals.…”

Section: Introductionmentioning

confidence: 99%

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A design protocol for tailoring ice-templated scaffold structure

Pawelec

Husmann

Best

et al. 2014

J. R. Soc. Interface.

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ResearchCite this article: Pawelec KM, Husmann A, Best SM, Cameron RE. 2014 A design protocol for tailoring ice-templated scaffold structure. J. R. Soc. In this paper, we show, for the first time, the key link between scaffold architecture and latent heat evolution during the production of porous biomedical collagen structures using freeze-drying. Collagen scaffolds are used widely in the biomedical industry for the repair and reconstruction of skeletal tissues and organs. Freeze-drying of collagen slurries is a standard industrial process, and, until now, the literature has sought to characterize the influence of set processing parameters including the freezing protocol and weight percentage of collagen. However, we are able to demonstrate, by monitoring the local thermal events within the slurry during solidification, that nucleation, growth and annealing processes can be controlled, and therefore we are able to control the resulting scaffold architecture. Based on our correlation of thermal profile measurements with scaffold architecture, we hypothesize that there is a link between the fundamental freezing of ice and the structure of scaffolds, which suggests that this concept is applicable not only for collagen but also for ceramics and pharmaceuticals. We present a design protocol of strategies for tailoring the ice-templated scaffold structure.

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“…In all cases, sample size was approximately 10 mg. Cooling and warming rates were 28C min 21 . The samples were initially held at 258C and cooled down to 2258C.…”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A design protocol for tailoring ice-templated scaffold structure

Pawelec

Husmann

Best

et al. 2014

J. R. Soc. Interface.

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“…This is because the bulk density of the LM product depends on the freezing step. Freezing determine the dimension and the shape of the ice crystals that form the structure of the frozen LM product (Kochs et al, 1993;Nakagawa et al, 2006;Searles et al, 2001). Regardless of the concentration of mannitol solution, the LM powders were solids occupying approximately the volume of the former solution.…”

Section: Density Porosity and Cohesivitymentioning

confidence: 99%

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

Kaialy

Mawlud

2016

International Journal of Pharmaceutics

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Mannitol is a pharmaceutical excipient that is receiving increased popularity in solid dosage forms. The aim of this study was to provide comparative evaluation on the effect of mannitol concentration on the physicochemical, mechanical, and pharmaceutical properties of lyophilised mannitol. The results showed that the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol powders are strong functions of mannitol concentration. By decreasing mannitol concentration, the true density, bulk density, cohesivity, flowability, netcharge-to-mass ratio, and relative degree of crystallinity of LM were decreased, whereas the breakability, size distribution, and size homogeneity of lyophilised mannitol particles were increased. The mechanical properties of lyophilised mannitol tablets improved with decreasing mannitol concentration. The use of lyophilised mannitol has profoundly improved the dissolution rate of indomethacin from tablets in comparison to commercial mannitol. This improvement exhibited an increasing trend with decreasing mannitol concentration. In conclusion, mannitols lyophilised from lower concentrations are more desirable in tableting than mannitols from higher concentrations due to their better mechanical and dissolution properties. Abbreviations∆H0, Endothermic enthalpy of CM melting; ∆Hs, Endothermic enthalpy of LM melting; ANOVA, One-way analysis of variance; API, Active pharmaceutical ingredient; c.opt, Optimal concentration; CI, Carr's index; CM, Commercial mannitol; Cman, Concentration of mannitol; d10%, particle size at 10% volume distribution; d50%, particle size at 50% volume distribution; d90%, particle size at 90% volume distribution; Db, Bulk density, DE, Dissolution efficiency; DSC, Differential scanning calorimeter; Dt, tap density; EB, Ease of breakage; Eq, Equation; FT-IR, Fourier transform infrared; GI, Gastro intestinal; HSD, Honestly Significant Difference; I, Relative intensity; Iamorphous, the input to the intensity from the amorphous region; Icrystalline, the input to the intensity from the crystalline region; LM, Lyophilised mannitol; MDR, Mean dissolution rate; MDT, Mean dissolution time; P, Statistical probability; PXRD, Powder X-ray diffraction; Q10min, The mean percentage of drug dissolved in the first 10 min; Q30min, The mean percentage of drug dissolved in the first 30 min; Q4min, The mean percentage of drug dissolved in the first 4 min; Q50min; The mean percentage of drug dissolved in the first 50 min; RDB, Relative degree of breakage;

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“…As a reduced pore size is associated with a higher dried product mass transfer resistance and vice versa, the sublimation rate during primary drying is highly influenced by the pore size in the dried layer 6 . Eventually, the uncontrolled freezing step causes vial-to-vial variability of the sublimation rate within a batch and between batches 8 . Primary drying requires appropriate and sufficient energy supply to the vial, necessary for ice sublimation 3 .…”

Section: Introductionmentioning

confidence: 99%

Noncontact Infrared-Mediated Heat Transfer During Continuous Freeze-Drying of Unit Doses

Bockstal

Meyer

Corver

et al. 2017

Journal of Pharmaceutical Sciences

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Recently, an innovative continuous freeze-drying concept for unit doses was proposed, based on spinning the vials during freezing. An efficient heat transfer during drying is essential to continuously process these spin frozen vials. Therefore, the applicability of non-contact infrared (IR) radiation was examined. The impact of several process and formulation variables upon the mass of sublimed ice after 15 minutes of primary drying (i.e., sublimation rate) and the total drying time was examined. Two experimental designs were performed in which electrical power to the IR heaters, distance between the IR heaters and the spin frozen vial, chamber pressure, product layer thickness and five model formulations were included as factors. A near-infrared (NIR) spectroscopy method was developed to determine the endpoint of primary and secondary drying. The sublimation rate was mainly influenced by the electrical power to the IR heaters and the distance between the IR heaters and the vial. The layer thickness had the largest effect on total drying time. The chamber pressure and the five model formulations had no significant impact on sublimation rate and total drying time, respectively. This study shows that IR radiation is suitable to provide the energy during the continuous processing of spin frozen vials.

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The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature‐controlled shelf

Cited by 335 publications

References 28 publications

A design protocol for tailoring ice-templated scaffold structure

A design protocol for tailoring ice-templated scaffold structure

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

Noncontact Infrared-Mediated Heat Transfer During Continuous Freeze-Drying of Unit Doses

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